Oral submucous fibrosis (OSF) is a well-recognised-potentially malignant condition of the oral cavity associated with areca nut chewing. Areca nut has been shown to have a high copper content compared to other commonly eaten nuts, and chewing areca nut for 5-30 min significantly increases soluble copper in whole mouth fluids. Our aims were to determine if tissue and serum concentrations of copper were raised in patients with OSF as a result of chewing areca nut. A panel of buccal mucosal biopsies from patients with OSF from Nagpur, India, was used to measure the tissue concentrations of copper by mass absorption spectrometry (MAS). By MAS, the mean tissue copper level was 5.5+/-2.9 microg/g in the OSF specimens (n=11) compared with 4+/-1.9 microg/g in the non-areca chewing controls (n=7) (P=0.2). Energy dispersive x-ray microanalysis (EDX) was used to identify the presence and distribution of the metal element. EDX showed distinct peaks corresponding to copper (Kalpha 8.04 keV; Kbeta, 8.91 keV) in the epithelium (21/23) and in the connective tissue (17/23) of the OSF specimens compared to spectra obtained from control oral biopsies from non-areca chewing subjects (n=7). These findings were confirmed by secondary ion mass spectrometry (SIMS) analysis in a small number of samples. Serum copper (17.23+/-1.80 pmol/l), caeruloplasmin (0.32+/-0.04 g/l) levels and urinary copper (0.52+/-0.26 micromol/l) in OSF patients (n=14) were within the laboratory reference ranges. The finding of copper in OSF tissue supports the hypothesis of copper as an initiating factor in OSF, playing a role in stimulating fibrogenesis by the upregulation of lysyl oxidase activity.

Patients with beta-thalassaemia major frequently suffer from hypersiderosis which leads to hemochromatosis of major organs such as the heart and liver. Little information exists about the ultrastructural pathology of the human heart in beta-thalassaemia patients. Five Cypriot patients with elevated blood ferritin and intractable heart failure were investigated. Cardiac biopsies from these patients were studied by light and electron microscopy, as well as by X-ray microanalysis. Ultrastructural examination revealed the presence of disrupted myocytes showing loss of myofibers, dense nuclei, and a variable number of pleomorphic electron dense granules. These cytoplasmic granules or siderosomes consisted of iron-containing particles as confirmed by X-ray microanalysis. It is likely that the ultrastructural changes observed in myocytes of patients with beta-thalassaemia are largely due to iron deposition.

Epivatianos A, Harrison JD, Garrett JR, Davies KJ, Senkus R. Ultrastructural and histochemical obseivations on intracellular and luminal tiiictocalculi in the feline sublingual salivaty gland. J Otal Pathol 1986: 15: 513-517.As the genesis of salivaiy calculi in man has not been established, the fortuitous observation of tnicrocalculi iti sublingual glarids of cats ptotnpted this study. Microcalculi wete seen occasionally within acinar cells and lutnina and macrophages, and rately intetstitially. Miciocalculi wete stained with the periodic-acid/Schilf technique, and acid-phosphatase activity was associated with intracellular microcalculi. Intracellular microcalculi were seen ultrastructurally in acinar cells in membrane-bound vacuoles that also contaiticd debris and sometimes what appeated to be secretory tnaterial. X-ray tnicroanalysis showed the mictocalculi to consist of crystals containing calciutn and phosphorus. The observations suggest that the tnicrocalculi fortn within autophagosotncs in acinar cells by a ptecipitatioti of calciutn and phosphorus ptesent in degenerate tnaterial, and that (he tniciocalculi eventually enter lutnina, whete they tnay be dischatgcd in the saliva or retaiticd and enlarge.

Ras isoforms have distinct and separate subcellular distributions in normal kidney cells. Understanding the functional aspects of this distribution pattern is essential if Ras is to be targeted by genetic or molecular therapeutic tools.